Environmental and nutritional exposures in-utero and early postpartum exert profound influences on the developing metabolic profile of an infant, impacting future risk of obesity. Rapid and excessive weight gain in the first 4-6 months of life, regardless of feeding mode, places an infant at elevated risk of later obesity. Bioactive components of human milk (HM) that may influence weight and adiposity gain remain unknown to a large extent. Furthermore, how maternal metabolic disorders such as obesity and diabetes, may impact the bioactive composition of HM, and how, in turn, this may influence infant growth remains largely unknown. The rise in prevalence in Type 2 diabetes (T2D) among pregnant and breastfeeding women has outstripped current knowledge of the impact this disease has on HM composition. This study will address this gap in knowledge. Exclusive breastfeeding is universally recommended for the first 6 months of life. Considering this recommendation, and the alarming prevalence of pediatric obesity, understanding how maternal obesity, with or without insulin resistance, may impact HM composition, and secondarily infant adiposity gain is of critical importance to addressing early risk factors for obesity. The over-arching hypotheses driving this research is that maternal metabolic dysfunction that accompanies obesity and T2D will impact the bioactive components of HM, and that these components will correlate with the rate of weight gain and body fat accumulated by the infant over a critical window of growth. Study Design: To address these essential questions, we will undertake a longitudinal cohort study and follow 60 well-characterized mother/infant pairs over the first 4 months of life, collecting longitudinal measures of breast milk composition and infant growth and body composition. We will follow 20 mother/infant pairs in each of the following study groups: normal weight (NW), overweight/obese (OW/Ob), and T2D women. The normo-glycemic OW/Ob group will allow us to distinguish the effects of maternal obesity alone vs. the impact of the insulin resistance of T2D, on HM composition and secondarily on infant growth. Aims: We will use the samples obtained to determine if maternal characteristics impact bioactive components of HM: inflammatory and oxidative load, adipokine, insulin, glucose, and caloric content of HM. We will also determine whether critical windows exist over these first 4 months of lactation when differences in HM between groups are more severe. Finally we will determine if these differences in HM composition are associated with the rate of infant weight and fat gain. Impact: Answers to these questions will have clinical implications for early post-natal feeding recommendations for high risk women and their infants. Identifying primary components of HM that associate with risky infant weight gain will provide an ideal avenue for intervention to optimize HM composition and minimize infant risk. Understanding the earliest post-natal risk factors that promote later obesity will identify opportunities to modify these influences, and thereby potentially interrupt the intergenerational transmission of obesity.